Hormones and Calcium Homeostasis

Key Hormones Influencing Animal Homeostasis

Overview of Today's Discussion

• Focus: Hormones influencing calcium homeostasis.
• Calcium significance in physiological processes will be covered.
• Key regulators: Thyroid and parathyroid hormones.
• Vitamin D: Peripheral involvement in calcium homeostasis.
• Mention of metabolic disorder (milk fever).

Plan for Tomorrow

• Cell signaling lecture: Linking hormones and cellular changes (including metabolism).
• Quick summary of endocrine components.
• Final exam discussion and case studies.

Hormones of the Thyroid and Parathyroid

• Parathyroid hormone.
• Calcitonin (thyrocalcitonin).
• Vitamin D.
• Source and roles of calcium.

Dysregulation Example: Milk Fever

• Metabolic disorder in cattle (especially dairy) and sometimes dogs.
• Occurs post-parturition or during lactation.
• Symptoms: Recumbency (lying down, unable to get up).
• Cause: Calcium dysregulation (hypocalcemia).
• Treatment: Intravenous calcium administration (into the milk vein).
• Rapid recovery after calcium administration, demonstrating the importance of calcium.

Calcium Homeostasis: Key Regulators

• Parathyroid Hormone.
• Calcitonin.
• Vitamin D.

Significance of Calcium

• About 1% of total body weight.
• Mainly as hydroxyapatite in bones (calcium phosphate).

Calcium Distribution

• 99% in bones as hydroxyapatite.
• Small amount in intracellular soft tissues.
• Small amount extracellularly.
• Bones act as a huge reservoir.

Calcium Regulation

• Calcium levels are closely managed in circulation and within cells due to its significant roles in normal physiology.

Roles of Calcium

• Muscle Contraction: Facilitates muscle contraction via release from the sarcoplasmic reticulum.
• Nerve Cell Conduction: Role in setting up membrane potentials for nerve signals.
• Exocytosis: Signaling role in molecule secretion.
• Enzyme Kinetics: Influences enzyme conformation through allosteric modifications; acts as a secondary signaler.
• Cell Membrane Stability: Influences stability.
• Bone and Teeth: Major component due to the high amount in these tissues.

Regulation Concept

• Balance between dietary intake, deposition in bone, and excretion from kidneys.

Summary Diagram

• Parathyroid hormone:
  • Released when calcium levels are low.
  • Effects: bone (mobilize Ca^{2+}), absorption (increase), excretion (reduce).
• Calcitonin:
  • Secreted when calcium levels are high.
  • Effects: bone (drives Ca^{2+} in), uptake (decrease), loss through kidneys (increase).

Parathyroid Hormone (PTH)

• Produced by parathyroid glands (small tissues in the neck, co-located with the thyroid).
• Peptide hormone: 84 amino acids.
• Quick synthesis and secretion rather than significant storage.
• Released when calcium concentration declines in circulation.
• Broken down in liver and kidneys.
• Short half-life (5-10 minutes) indicating fine regulation.

PTH Secretion Regulation

• Plasma calcium decline stimulates parathyroid glands to secrete PTH, increasing plasma calcium.
• Active inhibition: inverse relationship with calcitonin.
• Secretion is greatest when plasma calcium falls below 1 mM/L.

PTH Effects

• Increases calcium levels in extracellular fluids (including plasma).
• Acts on bone, kidneys, and gastrointestinal tract.
  • Low calcium \rightarrow PTH secretion \rightarrow calcium release from bone, absorption increase, excretion decrease.

PTH Effect on Bone

• PTH has receptors on osteoblasts, stimulating their differentiation into osteoclasts.
• Osteoclasts reabsorb calcium from bone.
• Osteoblasts lay down matrix and stimulate calcium absorption into bone.

PTH Effect on Kidneys

• Increases calcium reabsorption.
• Stimulates modification of vitamin D in kidneys (important for absorption in the gastrointestinal tract).

PTH Effect on Gastrointestinal Tract

• Decreased plasma calcium stimulates parathyroid glands \rightarrow PTH release.
• PTH acts on kidneys \rightarrow increased Ca^{2+} reabsorption and decreased urinary excretion.
• PTH stimulates modification of vitamin D in the kidneys.
• Modified vitamin D activates gastrointestinal epithelium to absorb more calcium.

Regulation of PTH Secretion

• Calcium levels in blood are the primary trigger.
• Magnesium levels also influence but less pronounced.
• Diurnal rhythm: elevation during sleep, highest in the morning.

Hyperparathyroidism

• Oversecretion of PTH.
• Caused by adenoma (neoplastic growth) in the parathyroid gland.
• Results in unregulated secretion.
• Effects: bone resorption, increased absorption in kidneys/gastrointestinal tract, bone morphology changes, fractures, teeth falling out, disrupted neural regulation.
• Symptoms include gastrointestinal motility changes (vomiting, constipation), depression, muscle weakness.

Hypoparathyroidism

• Low levels of PTH.
• Causes: genetic, immune-mediated, idiopathic.
• Inability to respond to lowering calcium concentrations.
• Symptoms: uncoordinated gait, muscle tremors/twitching, changes in behavior, seizures, lethargy.

Calcitonin

• Induces a decrease in calcium.
• Produced by parafollicular cells (C cells) of the thyroid.
• Small peptide (32 amino acids) with disulfide bridging.
• Produced as a pre-hormone, stored in granules, released by exocytosis.
• Basal level of secretion; increases when calcium levels increase.
• Gastrointestinal hormones influence calcitonin secretion (priming for anticipated calcium influx).

Calcitonin Effects

• Bone: Decreases movement of calcium from bone to extracellular fluids; inhibits osteoclasts.
• Gastrointestinal Tract:
  • Decreases calcium absorption
• Kidneys: Increases renal excretion of calcium.

Phosphate Balance

• Calcitonin influences phosphate availability.
• Excessive action of calcitonin can result in phosphate removal through renal excretion.

PTH and Calcitonin Together

• Bone is the main storage of calcium.
• Calcium level drops \rightarrow PTH secretion increases \rightarrow Calcium release from bone
• Calcium level high \rightarrow stimulation of thyroid parafollicular cells occurs \rightarrow calcitonin released to facilitate calcium reabsorption in bones

Vitamin D

• Sources: diet and ultraviolet (UV) light exposure to the skin, which stimulates cholesterol to become vitamin D3 (inactive form).
• Vitamin D is produced in the skin/diet and modified in the liver and kidneys to produce an active compound (1,25-dihydroxyvitamin D3).
• Modified form can be stored in adipose tissue because it's from cholesterol and is therefore lipophilic.
• Parathyroid hormone (PTH) regulates activation of vitamin D in the kidneys.
• Active vitamin D \rightarrow moves through the plasma membrane of the gastrointestinal tract where it can influence gene expression.
• Activation of mechanisms which facilitate calcium retention or calcium pumping from the gastrointestinal tract through to circulation.

Vitamin D Synthesis and Activation

• Sunlight \rightarrow Vitamin D3 formation \rightarrow liver enzymes and kidney enzymes modifies to change vitamin D confirmation \rightarrow resulting in active conformation \rightarrow facilitates calcium uptake in gastrointestinal tract

Abnormalities in Calcium Homeostasis: Hypocalcemia

• Common in dogs/dairy cows, especially near parturition.
• Mobilizing a lot of calcium for bone growth in fetus during pregnancy and also there is a drainage on lactation of calcium that binds milk proteins; calcium holds proteins in confirmation.
• Clinical emergency but easily reversed with calcium supplementation (e.g., calcium phosphate infusion).